MOTS-c
Also sold as: Mitochondrial Open Reading Frame of the 12S rRNA-c, MOTS-c acetate, MOTSc
MOTS-c is not on FDA's 503A bulk drug substances list, and FDA staff have proposed not adding either MOTS-c (free base) or MOTS-c acetate to it, ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026. FDA searched the published medical literature itself and identified no clinical studies and no human exposure data for MOTS-c by any route of administration; it states that potential safety risks in humans are therefore unknown, and that there is a lack of evidence to evaluate effectiveness for any of the uses MOTS-c was nominated for.
Which molecule this is. A mitochondrial-derived peptide of 16 amino acids, discovered in 2015. FDA evaluates two related substances: MOTS-c (free base) and MOTS-c acetate — different pharmaceutical ingredients, hence different bulk drug substances. FDA notes MOTS-c is a common name and not a USAN, and that it has encountered multiple salts and derivatives — including different active moieties — sold commercially under this same common name. DISTINGUISH FROM CB4211: CohBar's CB4211 is a modified ANALOG of MOTS-c, not MOTS-c. It is a different molecule, and its human exposure is not MOTS-c's human exposure. Conflating the two is the most likely honest error available on this compound — see the evidence note.
The FDA advisory committee vote, 23 July 2026
The Pharmacy Compounding Advisory Committee voted to recommend adding this substance to the 503A bulks list (7-5, two abstentions), against FDA’s own staff, who had recommended not adding it.
It is still not on the list. An advisory committee makes recommendations; it does not change what is permitted. We checked the 503A bulks list on 29 July 2026 and it is still dated 14 May 2026, with this substance absent from it. Adding a substance requires separate FDA action, which has not happened.
Vote tally reported by ABC News and other outlets; FDA had not published minutes or a transcript as of 29 July 2026, so there is no primary document for the tally yet. We will replace it with FDA’s own record when it publishes. The bulks-list status is from the primary document.
FDA status
FDA has not approved this and it is not in active development toward approval. That says nothing about whether it is being sold — most substances in this category are.
Not an FDA-approved drug for any indication, and not in active development toward approval. That says nothing about whether it is sold — it is.
503A compounding
The nominator withdrew the nomination. This is not a legalisation event — the substance is not on the 503A bulks list and remains non-compoundable.
Absent from Categories 1, 2 and 3 in the list updated 2026-05-14 — verified by fetching and text-extracting the document directly; the string 'MOTS' does not appear in it at all. Category 2 contains exactly six substances — Cesium Chloride, Domperidone, Germanium Sesquioxide, Ibutamoren Mesylate, Kisspeptin-10, and Quinacrine Hydrochloride for intrauterine administration — and MOTS-c is not one of them. Do not read that as reassurance: Category 2 is a list of substances FDA affirmatively found to raise significant safety risks, and staying off it means only that FDA has not made that finding, which on this substance is because nobody has looked in humans at all. The nomination — submitted by Wells Pharmacy Network, Document ID FDA-2015-N-3534-0293 — was withdrawn (withdrawal at Document ID FDA-2015-N-3534-0484). Withdrawal is not a legalisation event: MOTS-c did not enter Category 1, is not on the 503A bulks list, and remains non-compoundable. FDA is nonetheless evaluating both substances at its own discretion, and proposes not adding them. Category status is also not the criminal line — the Watkins indictment (D. Utah, 1:26-cr-00015, 2026-04-01) charges misbranding under 352(b), which is why Category 1 substances sit in the same indictment as non-listed ones.
Evidence
No randomised controlled trials in humans. Read the notes — the details matter more than the label.
Zero human administration studies of MOTS-c itself. This tier was assigned by checking what was ADMINISTERED, never by counting trials, and the count is where this compound traps people. MOTS-c appears to have several human RCTs; it has none. Spot-checked example: Nature Scientific Reports 2021 (PMC8376922), a secondary analysis of 49 breast cancer survivors in a 16-week supervised aerobic-and-resistance exercise trial, in which researchers reported that fasting plasma MOTS-c measured by in-house ELISA rose post-intervention in non-Hispanic White participants and did not change significantly in Hispanic participants. The intervention was EXERCISE; MOTS-c was the outcome measured, not the drug given. The same is true of the exercise-biomarker literature generally. FDA's own independent search agrees, and FDA characterises the nonclinical work as limited to in-vitro and in-vivo rodent models. THE NEAR-MISS, and note its source: CB4211 is an analog of MOTS-c, NOT MOTS-c. The FDA briefing document does not mention CB4211 or CohBar anywhere, so nothing in this paragraph comes from it. It comes from the ClinicalTrials.gov registry record NCT03998514 (https://clinicaltrials.gov/study/NCT03998514), which lists a Phase 1a/1b study of CB4211 in healthy non-obese subjects and subjects with nonalcoholic fatty liver disease, lead sponsor CohBar, Inc., enrollment 88 actual, overall status Completed, completion date 2021-04-19, with no results posted to the registry. That is human exposure to a DIFFERENT MOLECULE. It neither contradicts FDA's finding nor transfers to MOTS-c, and because no results were posted, the registry establishes only that the study ran and finished — not what it found. The precise statement is: no human administration data for MOTS-c; rodent and in-vitro only; one completed Phase 1, results unreported, in a related but distinct analog.
“We performed our own search of published medical literature and did not identify clinical studies evaluating administration of MOTS-c-related BDSs in human subjects.”Checked against the source on .
What FDA found
FDA’s own words. These are the most citable thing on this site, and the least likely to appear anywhere funded by someone selling the compound.
FDA staff propose not adding MOTS-c (free base) or MOTS-c acetate to the 503A Bulks List, ahead of the Pharmacy Compounding Advisory Committee meeting on 23-24 July 2026.
A staff proposal is not a final determination. The briefing document states: 'The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized.'
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“Accordingly, we propose not adding MOTS-c (free base) or MOTS-c acetate to the 503A Bulks List.”
Checked against the source on .FDA identified no clinical studies and no human exposure data for MOTS-c via any route of administration, and concludes that potential safety risks in humans are unknown.
The single most citable line on this compound, and one no vendor-funded page will ever print. 'Unknown' is the operative word — it is neither a clean bill of health nor a finding of harm. It means nobody has looked in humans. FDA's evidence cutoff is roughly March 2025 (its FAERS searches run through 2025-03-09), so this finding is scoped to what existed then; the CB4211 analog trial completed in 2021 and does not disturb it, because CB4211 is not MOTS-c.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“The nomination did not include, and FDA has not identified, any clinical studies or human exposure data for MOTS-c via any route of administration. Therefore, potential safety risks associated with the use of MOTS-c-related BDSs in humans are unknown.”
Checked against the source on .FDA did not evaluate ANY of the six nominated uses — insulin resistance, obesity, osteoporosis, vascular calcification, muscle/fat metabolism, longevity — because the nomination lacked sufficient information and FDA identified no clinical studies evaluating those uses.
Read footnote 4 before repeating the common claim that FDA 'assessed MOTS-c for obesity and osteoporosis and it fell short.' FDA declined to evaluate every single proposed use. Obesity and osteoporosis appear in the document only as context — as serious conditions with existing FDA-approved therapies — never as indications FDA assessed. This is an EVIDENTIARY VACUUM, NOT A REGULATORY LOOPHOLE. Footnote 3 notes that inclusion on the 503A Bulks List may not be limited to a specific use, so a 'do not add' outcome bars MOTS-c for ALL uses. The nomination cited 12 literature references; none was a clinical study.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“FDA did not evaluate the proposed uses: insulin resistance, obesity, osteoporosis, vascular calcification, muscle/fat metabolism, longevity because the nomination did not include sufficient information for the Agency to evaluate whether the substance is appropriate for these uses in compounded drug products. In addition, FDA did not identify clinical studies evaluating these uses of MOTS-c.”
Checked against the source on .FDA states that neither MOTS-c nor MOTS-c acetate has an applicable USP or National Formulary drug substance monograph, and that neither is a component of an FDA-approved drug.
This sentence lives in the PCAC briefing document, NOT in the 503A bulks list — the bulks list PDF contains neither the string 'MOTS' nor the string 'monograph'. Cite it accordingly. FDA separately searched the European Pharmacopoeia (11.5 edition, 2024) and the Japanese Pharmacopoeia (18th Edition) and found no monograph listings for either substance, and found no EMA-authorized products containing them.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“MOTS-c and MOTS-c acetate do not have an applicable USP or NF drug substance monograph and neither is a component of an FDA-approved drug.”
Checked against the source on .FDA concludes there is a lack of evidence to evaluate the effectiveness of the MOTS-c-related bulk drug substances for the nominated uses, because the nonclinical pharmacological studies were limited to in-vitro and in-vivo rodent models, dose-response assessments are missing, and the molecular targets are unknown.
Distinct from a finding of ineffectiveness, and the distinction is the whole point. FDA is not saying the MOTS-c-related BDSs failed; it is saying there is nothing to grade. Pair it with the fact that FDA declined to evaluate the six proposed uses at all — the effectiveness question was never reached because the evidence to reach it does not exist.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“There is a lack of evidence to evaluate the effectiveness of the MOTS-c-related BDSs for the nominated uses.”
Checked against the source on .FDA considers both MOTS-c (free base) and MOTS-c acetate NOT well-characterized physically and chemically, citing inconsistent naming conventions and missing data on impurities, aggregates, and microbial bioburden/bacterial endotoxin levels.
A product-identity finding independent of any efficacy question. FDA states that inconsistent naming 'represent[s] a safety risk for patients as they may be dosed with a different BDS than the physician ordered' — FDA has encountered multiple salts and derivatives, including different active moieties, sold under the common name 'MOTS-c'. The label on the vial may not name the molecule in the vial.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026Checked against the source on .FDA identified no in-vivo pharmacokinetic studies and no toxicology studies of MOTS-c of any kind — no acute toxicity, no repeat-dose toxicity, no genotoxicity, no developmental and reproductive toxicity, and no carcinogenicity studies.
The quoted sentence is one of five. FDA repeats the identical construction verbatim for repeat-dose toxicity, genotoxicity, developmental and reproductive toxicity, and carcinogenicity, and separately for in-vivo pharmacokinetic/toxicokinetic studies. Its summary: 'the nominator did not submit, and FDA did not identify nonclinical toxicity studies to inform safety considerations for potential clinical uses of MOTS-c (free base) or MOTS-c acetate.' This is the layer BENEATH the missing human data and it is the more surprising one — the animal safety package that would normally have to exist before a first human dose does not exist either. The rodent literature FDA reviewed is PHARMACOLOGY (does it do something), not TOXICOLOGY (does it harm). Those are different study types and the second set is empty.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“At the time of this evaluation, the nominator did not submit, and FDA did not identify acute toxicity studies of MOTS-c (free base) or MOTS-c acetate.”
Checked against the source on .FDA identified one pharmacokinetic-related study of MOTS-c — an in-vitro experiment in human whole blood, not an administration study — in which researchers reported that MOTS-c was rapidly broken down into shorter fragments, and FDA states it remains undetermined whether giving MOTS-c to humans can produce active concentrations at all.
The most under-reported finding in the document, and a threshold question the marketing skips entirely. In Knoop et al. 2019 — a doping-control assay development paper, not a trial — researchers incubated MOTS-c with human whole blood at 37°C and, using high resolution mass spectrometry, identified the truncated fragments MOTS-c(2-16), (3-16), (4-16) and (5-16); the authors stated the proteolytic hydrolysis was rapid and did not require long incubation. Blood in a tube is not a person, and the study administered nothing to anyone. But the implication FDA draws is the one that matters: before asking whether MOTS-c works in humans, it is not established that injected MOTS-c survives in humans long enough to do anything.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“It remains to be determined whether exogenous administration of MOTS-c to humans can generate pharmacologically active concentrations of the peptide over time.”
Checked against the source on .No outsourcing facility reported compounding any drug product containing MOTS-c (free base) or MOTS-c acetate to FDA between January 2017 and December 2025, and FDA states the earliest and extent of the substance's use in compounding is unknown.
Read this the way FDA scoped it, not more broadly. It covers 503B outsourcing facilities, which must report what they compounded; 503A compounders have no equivalent reporting duty, so the absence is not proof that nothing was compounded anywhere. It is evidence that the regulated, reporting tier of the compounding industry did not touch this substance for nine years. FDA separately found MOTS-c marketed online, including a holistic clinic stating it works with compounding pharmacies to obtain it and a wellness clinic promoting an IV 'cocktail' containing it — which is where the supply actually sits.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026Checked against the source on .FDA states the molecular target through which MOTS-c acts remains unknown, and that it is therefore difficult to predict which organs might be affected by it.
A mechanism finding that cuts against the confident mechanistic diagrams this compound is sold with. FDA accepts that AMPK signalling is involved — in Lee et al. 2015 the metabolic effects in high-fat-diet mice were not observed when the animals also received compound C, an AMPK inhibitor — but 'involved in' is not 'the target'. FDA adds that the rodent studies did not assess dose-response relationships, which is the other half of why it calls the clinical relevance of the nonclinical work unknown.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“In addition, while AMPK-dependent signaling appears to contribute to the pharmacological effects of MOTS-c, the molecular targets underlying the pharmacological effects of MOTS-c remain unknown making it difficult to predict which organs are likely to be affected by MOTS-c.”
Checked against the source on .
Documented safety signals
FAERS searches for MOTS-c adverse events through 2024-02-28, and again from 2024-02-26 through 2025-03-09, retrieved no reports.
An empty FAERS search is NOT a safety finding, and reading it as one inverts it. FDA attaches its own caveat: compounders under 503A generally do not report adverse events to FDA, and 'Unless an adverse event report is submitted to FDA, the Agency may not be aware of adverse events associated with a product compounded under section 503A.' Zero reports on a substance with zero human studies and a grey-market supply chain measures surveillance coverage, not safety.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026Checked against the source on .FDA cannot rule out immunogenicity risk, citing the potential for peptide aggregation and peptide-related impurities, and notes that subcutaneous administration is generally associated with increased immunogenicity compared with intravenous.
FDA identified no clinical studies assessing immunogenicity or aggregation of MOTS-c. Its stated concern is that consequences of an immune response 'may range from antibody responses with no apparent clinical manifestations to life-threatening and catastrophic reactions', and that neutralizing antibodies could neutralise the activity of the ENDOGENOUS peptide counterpart — a risk specific to peptides the body already makes.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“Based on available information, there are insufficient data to conclude that MOTS-c-related BDSs do not present these risks.”
Checked against the source on .MOTS-c is listed as a prohibited substance in the Global DRO Database, which draws on the 2024 World Anti-Doping Agency Prohibited List of Hormone and Metabolic Modulators.
Recorded as FDA recorded it. Prohibition by an anti-doping body is a sport-eligibility fact, not a finding of efficacy — a substance can be banned and still have no human evidence behind it, which is exactly the case here.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026Checked against the source on .
Questions people actually ask
Every answer cites the document behind it. Where the honest answer is “nobody knows”, that is the answer you will get.
- Is MOTS-c legal in 2026?
MOTS-c is not on FDA's 503A bulk drug substances list — the list of substances that may lawfully be used in pharmacy compounding — as of the list revised 14 May 2026, and it does not appear in any of that list's three categories. Being absent from the list is not a licence: it means MOTS-c has not been found appropriate for compounding, not that it has been cleared for it.
Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act — FDA, 14 May 2026Checked against the source on .- Did MOTS-c become legal again when the nomination was withdrawn?
No. The MOTS-c nomination was withdrawn by its nominator, Wells Pharmacy Network, and a withdrawal moves a substance sideways rather than toward legality: MOTS-c did not enter Category 1, did not join FDA's 503A bulk drug substances list, and remains outside the set of substances that may lawfully be used in compounding. FDA is in fact still evaluating both MOTS-c (free base) and MOTS-c acetate on its own initiative despite the withdrawal, and its staff have proposed not adding either substance to the list.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“The nomination was withdrawn, but because FDA is evaluating MOTS-c (free base) and MOTS-c acetate on its own initiative, FDA considered information submitted in this nomination as part of this evaluation.”
Checked against the source on .- Is there any human evidence that MOTS-c works?
No. FDA conducted its own search of the published medical literature and stated it did not identify clinical studies evaluating administration of MOTS-c-related bulk drug substances in human subjects, by any route. The studies in which MOTS-c was actually administered were, in FDA's characterisation, limited to in-vitro and in-vivo rodent models. FDA's conclusion is that there is a lack of evidence to evaluate the effectiveness of the MOTS-c-related bulk drug substances for the nominated uses.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“We performed our own search of published medical literature and did not identify clinical studies evaluating administration of MOTS-c-related BDSs in human subjects.”
Checked against the source on .- Is MOTS-c safe?
Nobody knows, and FDA says so directly: 'The nomination did not include, and FDA has not identified, any clinical studies or human exposure data for MOTS-c via any route of administration. Therefore, potential safety risks associated with the use of MOTS-c-related BDSs in humans are unknown.' The animal safety package is empty too — FDA identified no acute toxicity, repeat-dose toxicity, genotoxicity, reproductive toxicity or carcinogenicity studies of MOTS-c. FDA also states it cannot rule out immunogenicity risk from peptide aggregation and impurities. 'Unknown' is neither a clean bill of health nor a finding of harm: it means nobody has looked.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“Therefore, potential safety risks associated with the use of MOTS-c-related BDSs in humans are unknown.”
Checked against the source on .- Can I get MOTS-c from a compounding pharmacy?
MOTS-c is not on FDA's 503A bulk drug substances list, so it is not a substance that may lawfully be used in pharmacy compounding, and FDA staff have proposed not adding it. Outsourcing facilities — the registered 503B tier of compounders, which must report what they make — reported compounding no drug product containing MOTS-c (free base) or MOTS-c acetate to FDA between January 2017 and December 2025. FDA nonetheless found MOTS-c marketed online for injection, including by clinics stating they obtain it through compounding pharmacies, which is where the actual supply sits.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026Checked against the source on .- What did FDA propose at the July 2026 PCAC meeting about MOTS-c?
FDA staff proposed not adding MOTS-c (free base) or MOTS-c acetate to the 503A bulk drug substances list. The proposal appears in FDA's evaluation memorandum, internally dated 5/11/2026, inside the briefing package prepared for the Pharmacy Compounding Advisory Committee meeting of 23-24 July 2026. FDA gave four grounds: that neither substance is well-characterized physically and chemically, that their use in compounding is unknown, that no nonclinical data exist to inform safety for potential clinical uses, and that there are no clinical studies assessing safety or effectiveness in humans. A staff proposal is not a final determination — FDA states it will not issue one until the advisory committee process has been considered and all reviews finalized.
MOTS-c-Related Bulk Drug Substances — FDA Briefing Document, Pharmacy Compounding Advisory Committee Meeting, July 23-24, 2026 — FDA, 23 July 2026“Accordingly, we propose not adding MOTS-c (free base) or MOTS-c acetate to the 503A Bulks List.”
Checked against the source on .